A phase II trial of capecitabine in combination with the farnesyltransferase inhibitor tipifarnib in patients with anthracycline-treated and taxane-resistant metastatic breast cancer

An Eastern Cooperative Oncology Group Study (E1103)

Tianhong Li, Mengye Guo, William J. Gradishar, Joseph A. Sparano, Edith A. Perez, Molin Wang, George W. Sledge

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Capecitabine produces an objective response rate of up to 25 % in anthracycline-treated, taxane-resistant metastatic breast cancer (MBC). The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has clinical activity when used alone in MBC. The objective of this study was to determine the efficacy and safety of tipifarnib-capecitabine combination in MBC patients who were previously treated with an anthracycline and progressed on taxane therapy. Eligible patients received oral capecitabine 1,000 mg/m2 twice daily plus oral tipifarnib 300 mg twice daily on days 1-14 every 21 days. The primary endpoint was ORR. The trial was powered to detect an improvement in response rate from 25 to 40 %. Among 63 eligible, partial response occurred in six patients (9.5 %; 90 % CI 4.2-17.9 %), median progression-free survival was 2.6 months (95 % CI 2.1-4.4), and median overall survival was 11.4 months (95 % CI 7.7-14.0). Dose modifications were required for 43 patients (68 %) for either tipifarnib and/or capecitabine. Grades 3 and 4 toxicities were seen in 30 patients (44 %; 90 % CI 44.4-67.0 %) and 11 patients (16 %; 90 % CI 10.8-29.0 %), respectively. The most common grade 3 toxicities included neutropenia, nausea, and vomiting; and the most common grade 4 toxicity was neutropenia (8 out of 11 cases). The tipifarnib-capecitabine combination is not more effective than capecitabine alone in MBC patients who were previously treated with an anthracycline and taxane therapy.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalBreast Cancer Research and Treatment
Volume134
Issue number1
DOIs
StatePublished - Jul 2012

Fingerprint

tipifarnib
Farnesyltranstransferase
Anthracyclines
Breast Neoplasms
Neutropenia
Capecitabine
taxane
Nausea
Disease-Free Survival
Vomiting
Safety

Keywords

  • Capecitabine
  • Farnesyltransferase inhibitor
  • Metastatic breast cancer
  • Tipifarnib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase II trial of capecitabine in combination with the farnesyltransferase inhibitor tipifarnib in patients with anthracycline-treated and taxane-resistant metastatic breast cancer : An Eastern Cooperative Oncology Group Study (E1103). / Li, Tianhong; Guo, Mengye; Gradishar, William J.; Sparano, Joseph A.; Perez, Edith A.; Wang, Molin; Sledge, George W.

In: Breast Cancer Research and Treatment, Vol. 134, No. 1, 07.2012, p. 345-352.

Research output: Contribution to journalArticle

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abstract = "Capecitabine produces an objective response rate of up to 25 {\%} in anthracycline-treated, taxane-resistant metastatic breast cancer (MBC). The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has clinical activity when used alone in MBC. The objective of this study was to determine the efficacy and safety of tipifarnib-capecitabine combination in MBC patients who were previously treated with an anthracycline and progressed on taxane therapy. Eligible patients received oral capecitabine 1,000 mg/m2 twice daily plus oral tipifarnib 300 mg twice daily on days 1-14 every 21 days. The primary endpoint was ORR. The trial was powered to detect an improvement in response rate from 25 to 40 {\%}. Among 63 eligible, partial response occurred in six patients (9.5 {\%}; 90 {\%} CI 4.2-17.9 {\%}), median progression-free survival was 2.6 months (95 {\%} CI 2.1-4.4), and median overall survival was 11.4 months (95 {\%} CI 7.7-14.0). Dose modifications were required for 43 patients (68 {\%}) for either tipifarnib and/or capecitabine. Grades 3 and 4 toxicities were seen in 30 patients (44 {\%}; 90 {\%} CI 44.4-67.0 {\%}) and 11 patients (16 {\%}; 90 {\%} CI 10.8-29.0 {\%}), respectively. The most common grade 3 toxicities included neutropenia, nausea, and vomiting; and the most common grade 4 toxicity was neutropenia (8 out of 11 cases). The tipifarnib-capecitabine combination is not more effective than capecitabine alone in MBC patients who were previously treated with an anthracycline and taxane therapy.",
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